CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / Lectinas sÃo proteÃnas que contÃm pelo menos um domÃnio nÃo catalÃtico que se liga reversivelmente a mono ou oligossacarÃdeos especÃficos. Por serem capazes de âdecifrar os glicocÃdigosâ codificados na estrutura dos glicoconjugados, as lectinas sÃo molÃculas que possuem um grande potencial biotecnolÃgico e despertam um grande interesse cientÃfico. As Lectinas de Leguminosas representam o grupo mais bem estudado, contudo a maioria dos estudos de lectinas de leguminosas tem envolvido membros da subfamÃlia Papilionoideae, enquanto que investigaÃÃes de lectinas de outras duas subfamÃlias, Caesalpinoideae e Mimosoideae, sÃo escassas. Mesmo dentro da subfamÃlia Papilionoideae, a grande maioria dos estudos com lectinas se concentram em membros da tribo Phaseoleae, prinicpalmente das subtribos Diocleinae e Vicieae, enquanto que as outras tribos desta subfamÃlia ainda sÃo pouco exploradas. Neste contexto, o presente trabalho descreve a caracterizaÃÃo estrutural e biolÃgica das de duas novas lectinas purificadas de sementes de Parkia biglobosa (SubfamÃlia Mimosoideae, tribo Parkiae) e Vatairea guianensis Aublet (SubfamÃlia Papilionoideae, tribo Dalbergieae). Sementes de P. biglobosa possuem uma lectina (PBL) especÃfica para manose/glicose que foi eficientemente purificada por cromatografia de afinidade em gel de Sephadex G-100. PBL à composta por uma cadeia polipeptÃdica Ãnica, nÃo glicosilada e composta por trÃs domÃnios relacionados a jacalina organizados em sequÃncia. A lectina exibe atividade antiinflamatÃria que està associada à inibiÃÃo da migraÃÃo de leucÃcitos e uma atividade antiniciceptiva que pode estar associada à inibiÃÃo da dor inflamatÃria. PBL foi cristalizada e os dados produzidos nos experimentos de difraÃÃo do cristal por raios X possibilitarÃo a futura resoluÃÃo da estrutura tridimensional desta proteÃna. Com relaÃÃo a lectina especÃfica para N-acetil-D-galactosamina/D-galactose presente nas sementes de V. guianensis (VGL) foi evidenciado que esta exibe similaridade de estrutura primÃria com outras lectinas isoladas de espÃcies de plantas taxonomicamente relacionadas, tais como lectinas isoladas da tribo Sophoreae e a lectina VML, com a qual VGL compartilha o mesmo processamento pÃs- traducional. AlÃm disso, ficou evidente que VGL exibe um efeito vasorrelaxante in vitro em aortas de ratos, sendo que este efeito à dependente da presenÃa de endotÃlio, envolve a participaÃÃo do Ãxido nÃtrico e à mediado pelo sÃtio de ligaÃÃo a carboidratos da lectina. / Lectins are defined as structurally heterogeneous proteins of non-immune origin, possessing at least one non-catalytic domain by which they reversibly bind to specific mono- or oligosaccharides. By deciphering the codes present in the glycan structure, lectins are attracting increasing interest in biotechnology. The most studied group of carbohydrate-binding proteins consists of lectins purified from species of the Leguminosae family. Among the studies of the lectins from Leguminosae. many are focused on members of the Papilionoideae subfamily, while investigations of lectins of the other two subfamilies, Caesalpinioideae and Mimosoideae, are scarce. Even within the subfamily Papilionoideae, the vast majority of studies focus on lectins from Phaseoleae and Vicieae tribes, while the other tribes of this subfamily are still poorly explored. In this context, this work describes the structural and biological characterization of two new lectins purified from seeds of Parkia biglobosa (Mimosoideae subfamily, tribe Parkiae) and Vatairea guianensis Aublet (subfamily Papilionoideae, tribe Dalbergieae). P. biglobosa seeds (subfamily Mimosoidae) possess mannose/glucose-specific lectin (PBL) that was purified by affinity chromatography on a Sephadex G-100 column. PBL is composed by a single nonglycosylated polypeptide chain of three tandemly arranged jacalin-related domains and showed important antinociceptive activity associated to the inhibition of inflammatory process. PBL was crystallized and the data produced in the X-ray diffraction experiments will enable the future resolution three-dimensional structure of this protein. With respect to the N-acetyl-D-galactosamine/D-galactose specific lectin present in the V. guianensis seeds (VGL) was demonstrated that this protein presents high similarity in primary structure to other lectins from evolutionarily related plants, such as VML and lectins belonging to the Sophoreae tribe. VGL exhibits vasorelaxant activity in contracted rat aortas, an effect that is strictly dependent on the endothelium and involves NO and the lectin domain.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / Margaritopsis carrascoana is a small shrub belonging to the Rubiaceae family and endemic from northeastern of Brazil flora growing in the sandy soils of the region of Ibiapaba and Araripe plateaus â Cearà state. The absence of reports of phytochemical studies related to this species, combined with occurrence of bioactive alkaloids in the genus, motivated us to perform chemical study. The plant specimen was collected in Araripe plateu, in MoreilÃndia-PE county. The phytochemical investigation of the ethanolic extract from the stems yielded the alkaloids calycosidine, hodgkinsine, N-8â-formyl-calycosidine and N-8â-methyl-N-1â-desmethylisocalycosidine, besides neolignan dihydrodehydrodiconiferyl alcohol 4-O-β-D-glucopyranoside, the flavonol luteolin 7-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl, the triterpenes lupeol and ursolic acid, and the mixture of β-sitosterol and stigmasterol steroids, as aglycones and glycosylated. From the ethanolic extract of the leaves were isolated the flavonoid luteolin 7-O-[β-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside, chrysoeriol 7-O-[β-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside, luteolin 7-O-{β-D-apiofuranosyl-(1→6)-[β-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranosyl} and luteolin 7-O-{α-L-rhamnopyranosyl-(1→6)-[β-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranosyl}. The alkaloids N-8"-formyl-calycosidine, N-8â-methyl-N-1â-desmethylisocalycosidine, luteolin 7-O-{β-D-apiofuranosyl-(1→6)-[β-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranosyl} and luteolin 7-O-{α-L-rhamnopyranosyl-(1→6)-[β-L-rhamnopyranosyl-(1→2)]-β-D-glucopyra-nosyl}, are being reported for the first time in the literature, and the other secondary metabolites are unprecedented in the genus Margaritopsis. The secondary metabolites were isolated using classical chromatography techniques; including adsorption chromatography on silica gel, exclusion chromatography on Sephadex LH-20, reverse phase chromatography (C-18), and high performance liquid chromatography (HPLC). For structural characterization were used infrared spectroscopy, mass spectrometry and nuclear magnetic resonance techniques including uni (1H NMR and 13C NMR and DEPT 135) and two-dimensional experiments (HMBC, HSQC, COSY and NOESY), and comparison with the literature data. In addition, the flavonoids flavonol luteolin 7-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl, luteolin 7-O-[β-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside, luteolin 7-O-{β-D-apiofuranosyl-(1→6)-[β-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranosyl} and luteolin 7-O-{α-L-rhamnopyranosyl-(1→6)-[β-L-rhamnopyranosyl-(1→2)]-β-D-glucopyranosyl, sho-wed antioxidant activity greater than the BHT and quercetin standards, while ethanol extracts of stems and leaves showed inhibitory activity on the acetylcholinesterase enzyme. On the other hand, hodgkinsine showed potent cytotoxic activity against ovary, glioblastoma and colon cancer cells lines. The ethanol extract of the leaves and its alkaloidal fraction were submitted to nociception test and yielded good results. The ethanolic extract of the leaves was subjected to gastric antiulcer activity test, leading to a significant reduction in gastric lesions induced by ethanol in mice. / Margaritopsis carrascoana à um pequeno arbusto pertencente à famÃlia Rubiaceae e endÃmico da flora do Nordeste brasileiro, que cresce em solos arenosos do planalto da Ibiapaba e serra do Araripe - CearÃ. A ausÃncia de relatos acerca de estudos fitoquÃmicos relacionados à espÃcie, aliada a ocorrÃncia de alcalÃides bioativos no gÃnero, nos motivou ao seu estudo quÃmico. Desta forma, o espÃcimen vegetal foi coletado na chapada do Araripe, municÃpio de MoreilÃndia-PE. A investigaÃÃo fitoquÃmica do extrato etanÃlico dos talos resultou no isolamento dos alcalÃides calicosidina, hodgkinsina, N-8â-formilcalicosidina e N-8â-metil-N-1â-desmetilisocalicosidina, da neolignana Ãlcool 4-O-β-D-glicopiranosil-di-hidro-desidrodiconiferÃlico, do flavonÃide 7-O-[α-L-ramnopiranosil-(1→2)-β-D-glicopiranosil luteolina, dos triterpenos lupeol e o Ãcido ursÃlico, e da mistura de esterÃides β-sitosterol e estigmasterol, como agliconas e nas formas glicosiladas. A partir do estudo do extrato etanÃlico das folhas foram isolados os flavonÃides 7-O-[β-D-glicopiranosil-(1→6)-β-D-apiofuranosil] luteolina, 7-O-[β-D-glicopiranosil-(1→6)-β-D-apiofuranosil] crisoeriol, 7-O-{β-D-apiofuranosil-(1→6)-[α-L-ramnopiranosil-(1→2)-β-D-glicopiranosil} luteolina e 7-O-{α-L-ramnopiranosil - (1→6) - [α-L-ramnopiranosil-(1→2)-β-D-glicopiranosil} luteolina. Os alcalÃides N-8â-formilcalicosidina e N-8â-metil-N-1â-desmetilisocalicosidina, e os flavonÃides 7-O-{β-D-apiofuranosil-(1→6)-[α-L-ramnopiranosil-(1→2)-β-D-glicopiranosil} luteolina e 7-O-{α-L-ramnopiranosil-(1→6)-[α-L-ramnopiranosil-(1→2)-β-D-glicopiranosil} luteolina, estÃo sendo relatados pela primeira vez na literatura, enquanto todas as demais substÃncias possuem carÃter inÃdito no gÃnero Margaritopsis. O isolamento dos metabÃlitos secundÃrios foi conduzido atravÃs de tÃcnicas cromatogrÃficas clÃssicas, incluindo cromatografia de adsorÃÃo em gel de sÃlica, cromatografia por exclusÃo molecular em Sephadex LH-20, cromatografia de fase reversa (C-18) e cromatografia lÃquida de alta eficiÃncia (CLAE). Para a caracterizaÃÃo estrutural foram utilizadas tÃcnicas espectroscÃpicas utilizando infravermelho, espectrometria de massas e ressonÃncia magnÃtica nuclear, incluindo tÃcnicas uni (RMN 1H e RMN 13C e DEPT 135) e bidimensionais (HMBC, HSQC, COSY e NOESY), alÃm de comparaÃÃo com dados descritos na literatura. Em adiÃÃo, os flavonÃides 7-O-[α-L-ramnopiranosil-(1→2)-β-D-glicopiranosil luteolina, 7-O-[β-D-glicopiranosil-(1→6)-β-D-apiofuranosil] luteolina, 7-O-{β-D-apiofuranosil-(1→6)-[α-L-ramnopiranosil-(1→2)-β-D-glicopiranosil} luteolina e 7-O-{α-L-ramnopiranosil-(1→6) - [α-L-ramnopiranosil-(1→2)-β-D-glicopiranosil} luteolina apresentaram atividade antioxidante maior que os padrÃes BHT e quercetina, enquanto os extratos etanÃlicos dos talos e folhas apresentaram atividade inibidora da enzima acetilcolinesterase. Por outro lado, o alcaloide hodgkinsina apresentou potencial citotÃxico frente Ãs cÃlulas de ovÃrio, glioblastoma e colon. No teste de nocicepÃÃo, realizado com o extrato etanÃlico das folhas e a fraÃÃo alcalÃidica, foram observados resultados positivos para ambas as fraÃÃes. O extrato etanÃlico das folhas foi submetido a teste de atividade antiÃlcera gÃstrica, levando a uma reduÃÃo significativa da Ãrea de lesÃo gÃstrica induzida pelo etanol em camundongos.

Muitas espécies de Gracilaria são de importância econômica devido à exploração do ágar e, em menor escala, por serem consumidas diretamente na alimentação. Recentemente pesquisas têm mostrado um bom potencial biológico dessas espécies, porém com pouca investigação relacionada a identificação das substâncias bioativas. Sob esta perspectiva, o objetivo geral deste estudo foi investigar os componentes químicos majoritários e avaliar o potencial biológico e nutricional de três espécies nativas obtidas no litoral do nordeste brasileiro: Gracilaria birdiae E. M. Plastino & E. C. Oliveira Gracilaria caudata J. Agardh e Gracilaria domingensis (Kützing) Sonder ex Dickie. A análise da composição química levou a identificação de cerca de 50 substâncias distribuídas em alcanos, ácidos graxos livres, monossacarídeos, ácidos sulfônicos, aminoácidos livres, esteróis, heterosídeos, lipídios polares, monoacilgliceróis, polissacarídeos sulfatados, aminoácidos do tipo micosporinas e sais halogenados. Ésteres de ácidos graxos, ácidos carboxílicos aromáticos, fitol e o derivado fitona, diidroactinidiolideo também foram detectados em pequenas quantidades. Gracilaria caudata e G. domingensis foram muito semelhantes quimicamente. Já G. birdiae foi menos diversa, compartilhando, porém, muitas das substâncias majoritárias. Os resultados desse trabalho sugerem grande diversidade química para espécies de Gracilaria, ampliando o conhecimento disponível para Rhodophyta. Atividades biológicas promissoras foram detectadas para diversos ensaios. O extrato hexânico de G. caudata foi ativo frente as artêmias, com o isolamento biomonitorado de duas possíveis substâncias bioativas. O isolamento biomonitorado guiado pela atividade bioestimulante in vitro de plântulas de Lactuca sativa L. (alface) resultou no ácido palmítico como sendo responsável pelo aumento em 83% do crescimento de raiz. Os polissacarídeos sulfatados presentes nos extratos aquosos de G. caudata e G. domingensis foram bioestimulantes de raiz e folha de alface. Além disso, esses polissacarídeos de G. domingensis inibiu a atividade da enzima transcriptase reversa do HIV-1. Para G. birdiae vários extratos se mostraram com potenciais citotóxico e fitotóxico. Os aminoácidos tipo micosporinas (asterina 330, chinorina, palitina, palitinol e porphyra 334), por serem substâncias comuns em algas vermelhas, foram isolados e avaliados quanto ao potencial biológico. A palitina inibiu a atividade da enzima transcriptase reversa do HIV-1, enquanto porphyra 334, chinorina e também palitina apresentaram boa atividade antioxidante com o ensaio do reagente Folin-Ciocalteu. Quanto ao aspecto nutricional, os resultados indicaram que as três algas avaliadas, principalmente G. birdiae, foram ricas em fibras dietéticas e sais minerais, formando um grupo alimentar único bem diferente dos alimentos tradicionais na mesa dos brasileiros. Em resumo, os resultados obtidos para as espécies de Gracilaria avaliadas reforçaram a ideia de ampla diversidade química para as rodófitas, mostraram resultados promissores em diferentes ensaios, além de apontarem um potencial uso como fonte suplementar nas dietas dos brasileiros / Many Gracilaria species are economically important due to the exploitation of agar and, to a lesser extent, because they are consumed directly in the food. Recent studies have shown a good biological potential of these species, but with few studies aimed at the identification of bioactive substances. From this perspective, the general objective of this study was to investigate the major chemical components and to evaluate the biological and nutritional potential of three native species obtained in the northeast Brazilian coast: Gracilaria birdiae E. M. Plastino & E. C. Oliveira Gracilaria caudate J. Agardh and Gracilaria domingensis (Kützing) Sonder ex Dickie. The chemical composition analysis resulted in the identification of about 50 metabolites distributed as alkanes, free fatty acids, monosaccharides, sulfonic acids, free amino acids, sterols, heterosides, polar lipids, monoacylglycerols, sulfated polysaccharides, mycosporine-like amino acids and halogenated salts. Esters of fatty acids, aromatic carboxylic acids, phytol and the phytone derivative, dihydroactinidiolide were also detected in small amounts. G. caudate and G. domingensis were chemically similar. On the other hand G. birdiae was less diverse, sharing, however, many of the major metabolites. The results of this work suggest a great chemical diversity for Gracilaria species, increasing the knowledge available for Rhodophyta. Promising biological activities were detected for several assays. The hexane extract of G. caudate was active in brine shrimp lethality assay, with the biomonitoring isolation of two possible bioactive substances. The biomonitoring isolation guided by in vitro biostimulant activity of young Lactuca sativa L. (lettuce) seedlings resulted in palmitic acid as responsible for 83% increase in root growth. The sulfated polysaccharides present in the aqueous extracts of G. caudate and G. domingensis were biostimulant of root and lettuce leaf. In addition, these polysaccharides from G. domingensis inhibited the activity of the HIV-1 reverse transcriptase enzyme. For G. birdiae several extracts showed cytotoxic and phytotoxic potentials. Mycosporine-like amino acids (asterina 330, shinorine, palythine, palythinol and porphyra 334), known as common red algae substances, were isolated and evaluated for biological potential. Palythine inhibited the activity of the HIV-1 reverse transcriptase enzyme, while porphyra 334, shinorine and palythine showed good antioxidant activity using the Folin-Ciocalteu reagent assay. Regarding the nutritional aspect, the results indicated that from the three algae evaluated, highlighting G. birdiae, all were rich in dietary fibers and minerals, forming a unique food that is very different from the traditional Brazilian food. In summary, the results obtained for the Gracilaria species studied reinforced the idea of a wide chemical diversity for red algae, showing promising results in different bioassays, besides indicating a potential use as a supplementary food source in Brazilian diets

Les maladies impliquant des micro-organismes représentent un problème majeur de santé publique en raison du fort taux de mortalité provoqué par l'accroissement et l'émergence de souches résistantes. De même, les régions tropicales du Monde et La Réunion doivent faire face depuis plusieurs années à la pression accrue d'arthropodes ravageurs de cultures et vecteurs de maladies. Pour lutter contre ces arthropodes, les pesticides synthétiques aux conséquences désastreuses sur l'Homme et l'environnement sont principalement utilisés. Depuis quelques années, on observe un phénomène grandissant de résistance aux molécules conventionnelles à la fois chez les micro-organismes et les arthropodes. Face à ce constat, il est primordial de proposer de nouvelles molécules bioactives capables de lutter efficacement contre les ravageurs et les micro-organismes. Dans ce cadre, un criblage préliminaire réalisé sur vingt plantes endémiques et indigènes de La Réunion a permis de mettre en évidence l'activité antibactérienne et acaricide des extraits acétate d'éthyle de plusieurs espèces végétales. En raison de son large spectre d'activités biologiques, Peperomia borbonensis Miq. (Piperaceae), a été sélectionnée pour une investigation chimique et biologique approfondie. La suite de nos travaux a été consacrée à l'isolement et la caractérisation des métabolites secondaires de l'extrait apolaire de cette espèce. Les fractionnements bio-guidés réalisés ont conduit à l'isolement de quatorze molécules dont un amide à la structure nouvelle. Par ailleurs, l'étude de la fraction volatile de cette espèce a montré le potentiel insecticide de l'huile essentielle des feuilles pour lutter contre la mouche du melon B. cucurbitae. / The emergence of resistant strains in infectious diseases is a major public health issue. Similarly, arthropods which caused important economic damages in tropical and subtropical areas are continuously developing resistance to chemicals. To counteract this situation, it is essential to find new bioactive molecules able to fight pests and micro-organisms. In this context a preliminary screening was performed on twenty endemic plants and native of Reunion. Twenty-six ethyl acetate extracts were tested for their antibacterial and acaricidal activities. Considering its broad spectrum of activity, Peperomia borbonensis Miq. (Piperaceae), was selected for further chemical and biological investigations. Two bio-guided fractionations were performed on its apolar extract and let to the isolation of fourteen molecules. Moreover, the study of the volatile fraction has shown the insecticidal potential of the leaf essential oil of P. borbonensis against the melon fly B. cucurbitae.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-04-18T13:17:39Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese Tiago Araújo.compressed.pdf: 7089899 bytes, checksum: 0d9fa1d7f42954a36ff78b4171da7ef7 (MD5) / Made available in DSpace on 2016-04-18T13:17:39Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese Tiago Araújo.compressed.pdf: 7089899 bytes, checksum: 0d9fa1d7f42954a36ff78b4171da7ef7 (MD5) Previous issue date: 2015-04-30 / CAPEs / O presente estudo teve como objetivo investigar a relação entre hiperuricemia, distúrbios metabólicos e as atividades biológicas de Myrciaria cauliflora, Crataeva tapia e Indigofera suffruticosa. Para tanto, foi realizado inicialmente um estudo populacional, com 3620 voluntários, adultos, homens, não diabéticos, do Nordeste brasileiro. Obesidade abdominal e hipertrigliceridemia foram avaliadas para a identificação do fenótipo denominado Cintura Hipertrigliceridêmica (CHTG) e para a avaliação da influência desses distúrbios metabólicos sobre a hiperuricemia. Posteriormente, estudos com modelo animal (Mus musculus) foram conduzidos. Assim, extratos orgânicos (etéreo, acetônico e metanólico) foram preparados a partir do epicarpo de frutos maduros de M. cauliflora, denominados, sequencialmente, de MCEE, MCAE e MCME, nas concentrações de 200mg/Kg e de 400mg/Kg. Análise fitoquímica e estudo da toxicidade oral desses extratos foram realizadas. MCAE foi administrado durante 14 dias em camundongos com diabetes induzida por aloxana; e avaliação do perfil glicídico, lipídico, de função renal e hepática e análise histológica do pâncreas foram realizadas. Atividade anti-hiperuricêmica de MCAE, em modelo de oxonato de potássio, também foi investigada. MCEE, MCAE e MCME foram usados para a avaliação de: atividade anti-inflamatória, usando os modelos de edema de pata e de peritonite; atividade antinociceptiva, nos modelos de dor induzida por ácido acético e de placa quente; atividade antioxidante, por ensaio com 2,2-difenil-β- picrilhidrazil; e atividade antitumoral, contra tumor sólido de carcinoma de Ehrlich. Lectina de C. tapia foi purificada e testada para avaliação de atividade hipoglicêmica. Extratos etéreo, clorofórmico e acetônico de folhas de I. suffruticosa foram preparados, analisados fitoquimicamente e testados contra cepas de S. aureus. Como principais resultados, este estudo demonstrou que: obesidade abdominal e hipertrigliceridemia, isoladas, mostraram significativas razões de chance (RC) sobre a presença de hiperuricemia, porem o fenótipo CHTG demonstrou o maior efeito (RC = 4,3), especialmente após o uso dos pontos de corte obtidos especificamente para a população do estudo; hiperuricemia apresentou uma forte associação com alto risco de morte por evento cardiovascular em dez anos (RC = 3,5); 200mg/Kg/dia e 400mg/Kg/dia de MCAE causou uma redução significativa da glicose plasmática e redução nos níveis séricos de triglicerídios, uréia, creatinina e transaminases, aumento de HDL-colesterol, melhora do aspecto morfológico das ilhotas pancreáticas e diminuição de cerca de 50% nos níveis de ácido úrico; MCEE, MCAE e MCME apresentaram relevante atividade antioxidante e produziram reduções significativas da resposta inflamatória, de nocicepção e da massa tumoral; lectina de C. tapia provocou redução significativa nos níveis de glicose, melhora das funções e dos aspectos morfológicos dos rins, pâncreas e fígado de camundongos diabéticos; o extrato acetônico de folhas de I. suffruticosa foi um potente inibidor de S. aureus, seguido pelo extrato clorofórmico, melhorando também sinergisticamente o efeito da eritromicina. Portanto, hiperuricemia está bastante relacionada com o fenótipo CHTG em homens do Nordeste do Brasil, podendo elevar em muito o risco cardiovascular desses indivíduos. M. cauliflora demonstrou um grande potencial terapêutico para hiperuricemia e as condições metabólicas associadas e, assim como lectina de C. tapia, demonstrou ser um agente promissor para o tratamento da diabetes; enquanto que I. suffruticosa mostrou-se ser bastante promissora contra S. aureus. / This study aimed to investigate the relationship among hyperuricemia, metabolic disorders and the biological activities of Myrciaria cauliflora, Crataeva tapia e Indigofera suffruticosa. Therefore, it was initially performed a population study, with 3620 volunteers, adults, men, non-diabetic, from northeastern Brazil. Abdominal obesity and hypertriglyceridemia were evaluated for the identification of phenotype referred as Hypertriglyceridemic Waist (HTGW) and to assess the influence of these metabolic disorders hyperuricemia. Later, animal model studies (Mus musculus) were conducted. Thus, organic extracts (ether, acetone, and methanol) were prepared from ripe fruit epicarp of M. cauliflora referred to, sequentially, MCEE, MCAE, and MCME, at concentrations of 200mg/Kg and 400mg/Kg. Phytochemical analysis and study of oral toxicity of these extracts were made. MCAE was administered for 14 days in mice with alloxan-induced diabetes; and evaluation of glucose profile, lipid, renal and hepatic function and histological analysis of the pancreas were performed. Anti-hyperuricemic activity of MCAE, in potassium oxonate model, was investigated. MCEE, MCAE, and MCME were used for evaluation of: anti-inflammatory activity, using the rat paw edema model and peritonitis; antinociceptive activity, in models of pain induced by acetic acid and hot plate; antioxidant activity, by 2,2-diphenyl-β-picrylhydrazyl assay; and antitumor activity against solid tumor of Ehrlich carcinoma. Lectin of C. tapia was purified and tested for evaluation of hypoglycemic activity. Ether, chloroform and acetone extracts of leaves of I. suffruticosa were prepared, phytochemically analyzed and tested against strains of S. aureus. As main results, this study demonstrated that: abdominal obesity and hypertriglyceridemia, isolated, showed significant odds ratios (OR) for the presence of hyperuricemia, but HTGW phenotype demonstrated the most effect (OR = 4.3), especially after use the cutoffs obtained specifically for the study population; hyperuricemia showed a strong association with high risk of cardiovascular events death in ten years (OR = 3.5); 200mg/Kg/dia and 400mg/Kg/dia of MCAE caused a significant reduction in plasma glucose and reduction in serum levels of triglycerides, urea, creatinine and transaminases, increase in HDL-cholesterol, improvement in the morphological appearance of the pancreatic islets and decrease about 50% in the levels of uric acid; MCEE, MCAE, and MCME presented significant antioxidant activity and produced significant reductions in the inflammatory response, nociception and of the tumor mass; C. tapia lectin caused a significant reduction in glucose levels, improved the function and morphology of the kidneys, pancreas and liver of diabetic mice; and the acetone extract from the leaves of I. suffruticosa was a potent inhibitor of S. aureus followed by chloroform extract, also synergistically improving the effect of erythromycin. Therefore, hyperuricemia is closely related to the HTGW phenotype in men in Northeast Brazil, and can significantly increase the cardiovascular risk of these individuals. M. cauliflora demonstrated a great therapeutic potential for hyperuricemia and associated metabolic conditions, as well as C. tapia lectin proved to be a promising agent for the treatment of diabetes; while I. suffruticosa shown to be quite promising against S. aureus.

Ce travail de thèse consacré à la chimie de Zingiberaceae est divisé en deux parties distinctes.Dans la première partie, une étude phytochimique des rhizomes d’une plante africaine, Aframomum sceptrum K. Schum., couramment employée en Côte d’Ivoire, a été réalisée. Deux nouveaux composés, nommés sceptrumlabdalactone A et sceptrumlabdalactone B ont été isolés. Ce sont des composés terpéniques type labdane. Le sceptrumlabdalactone B est fortement actif contre L. donovani, avec une CI50 proche de celle de la pentamidine.L’extraction de l’huile essentielle des rhizomes a également été réalisée par hydrodistillation. L’analyse de l’huile par GC-MS a montré la présence de mono- et de sesquiterpènes avec une quasi-absence de monoterpènes aromatiques. L’évaluation des activités biologiques de l’huile a montré une activité contre les bactéries à Gram positif, et dans une moindre mesure, contre les bactéries à Gram négatif. Une forte activité trichomonicide a aussi été constatée.La deuxième partie, est consacrée à la curcumine. Ce diarylheptanoïde, est fréquent dans plusieurs Curcumas, Des analogues originaux, par exemple prénylés ont été préparés. Plusieurs activités biologiques (activités antiparasitaires, antibactériennes, anti-inflammatoires, anti-agrégation de la protéine β-amyloïde) ont été évaluées in vitro. L’activité anti-inflammatoire apparait différente de celle du produit de départ pour un des analogues.De même, la désaromatisation oxydante de la curcumine et ses analogues a permis l’accès en une ou deux étapes à des composés originaux à pharmacophore largement modifié.Des nanoparticules à base de "curcumine-squalénisée" ont également été préparées afin de surmonter le problème de la faible biodisponibilité de la curcumine. L’activité leishmanicide in vitro semble prometteuse. / During our research for fighting human African trypanosomiasis (sleeping sickness), two approaches were employed; firstly the traditional use of plants, secondly the synthesis of original derivatives of curcumin.In the first part, a bioguided fractionation of a methanolic extract of the rhizomes of Aframomum sceptrum K. Schum (Zingiberaceae) allowed the isolation of five compounds, including new labdanes, named sceptrumlabdalactone A and sceptrumlabdalactone B successively. Sceptrumlabdalactone B was reasonably active against T. brucei brucei, and strongly active against L. donovani, with IC50 close to that of pentamidine.The essential oil from the rhizomes of the species might also contribute to its biological activity. It was obtained by hydrodistillation and analyzed by GC–MS. Its major constituents were β-pinene, caryophyllene oxide and cyperene. It exhibited strong bactericidal activity against Gram-positive bacteria. It only showed moderate bacteriostatic activity against Gram-negative bacteria. Remarkable activities against T. b. brucei and Trichomonas vaginalis were also observed.The second part is devoted to curcumin. This diarylheptanoid, is common in several Curcuma spp.Structural modifications and preparation of nanoparticles of curcumin were carried out to increase its activities and/or overcome the problem of the low bioavailability of this compound.Original analogs, e.g. prenylated curcumins were prepared. Several biological activities (antiparasitic, anti-inflammation, Inhibition of β–amyloid aggregation, etc) were evaluated in vitro.Similarly, the oxidative dearomatization of curcumin and its analogues allowed the access to novel original compounds.Finally, the coupling of curcumin and squalene was achieved. The resulting molecules were able to form spherical nanoassemblies that may overcome bioavailability issues. Antiparasitic, antibacterial, and cytotoxic activities were also evaluated. The in vitro leishmanicidal activity seems promising.

As estruturas e propriedades biológicas das amidas piplartina e a piperina, isoladas respectivamente de Piper tuberculatum e P. nigrum, inspiraram a síntese de 89 derivados e 7 esters estruturalmente relacionadas. As preparações envolveram metodologias tradicionais e os compostos purificados tiveram suas estruturas caracterizadas por análises espectroscópicas e espectrométricas. Os estudos de fragmentação por IE e IES indicaram a clivagem preferencial da ligação N-CO no caso das cinamamidas, dienamidas e cinamimidas. Estudos computacionais envolvendo afinidade protônica e energias de ligação confirmaram a fragmentação preferencial da ligação amídica para as amidas. A citotoxicidade de 89 substâncias foi avaliada contra três células leucêmicas (K562, Nalm6 e Raji) e a partir dos valores de IC50 foram realizados estudos de relação estrutura-atividade (SAR). As linhagens K562 e a Nalm6 foram a mais resistente e vulnerável, respectivamente, e as amidas piplartina (1a), N-Ciclohexil-N-(ciclohexilcarbamoil)-3-(3,4,5-trimetoxifenil)propanamida (1n), e (E)-N,N-dibutil-3-(3,4-dimetoxifenil)acrilamida (13h) foram as mais ativas com IC50 de 0,34 µM; 0,84 µM e 1,88 µM contra K562 e (E)-N-ciclohexil-N-(ciclohexilcarbamoil)-3-(3,4-dimetoxifenil)acrylamida (13i) com IC50 de 0,98 µM contra Nalm6. A avaliação de atividade leishmanicida de 18 substâncias não se mostrou promissora. As abordagens qualitativas e quantitativas foram feitas baseadas nos descritores moleculares gerados pelo programa VolSurf+. A partir de métodos quimiométricos tais com PLS, algoritmo genético, árvores de decisão foi possível gerar modelos para correlacionar às propriedades moleculares com a atividade biológica. As propriedades de absorção, distribuição, metabolismo e excreção e os equilíbrios entres as regiões hidrofílicas e hidrofóbicas foram importantes para atividade citotóxica. O estudo de ancoragem molecular mostrou que as amidas (E)-N,N-dibutil-3-(3,4,5-trimetoxifenil)acrilamida (1l), 1n, (E)-3-(4-clorofenil)-N-ciclohexil-N-(ciclohexilcarbamoil)acrilamida (5a), 13h e 13i podem atuar como inibidores das histonas desacetilases particularmente HDAC4 e HDAC8. / The structures and biological properties of the amides piplartine and piperine isolated from Piper tuberculatum and P. nigrum respectively, inspired the synthesis of derivatives 89 and 7 esters structurally related. Their preparations were achieved using classical procedures and the purified amides were submitted to spectroscopic and spectrometric characterization. The study of fragmentation process by EI and ESI suggested the preferential cleavage of the N-CO bond of cinnamamides, dienamides and cinnamimides. The cytotoxicity of 89 compounds was evaluated against three leukemic cells (K562, Nalm6 and Raji) and based on IC50 values the structure-activity relationship (SAR) was performed. While the K562 and Nalm6 cells were the more resistant and more sensitive, respectively, the amides piplartine (1a), N-cyclohexyl-N-(ciclohexylcarbamoyl)-3-(3,4,5-trimethoxyphenyl)propanamide (1n) and (E)-N,N-dibutyl-3-(3,4-dimethoxyphenyl)acrylamide (13h) were in general the most active with IC50 of 0.34 µM, 0.84 µM and 1.88 µM against K562 and (E)-N-cyclohexyl-N-(ciclohexylcarbamoyl)-3-(3,4-dimethoxyphenyl)acrylamide (13i) with IC50 of 0.98 µM against Nalm6. The evaluation of leishmanicidal activity of 18 substances was also performed but was not promising. Qualitative and quantitative approaches were made based on molecular descriptors generated by VolSurf+ program. The chemometric methods such as PLS, genetic algorithm, decision trees generated models to correlate molecular properties with the biological activity. The absorption, distribution, metabolism and excretion properties and a balance between hydrophilic and hydrophobic moieties of the amides were important for an optimized activity. The molecular docking revealed that amides such as (E)-N,N-dibutyl-3-(3,4,5-trimethoxyphenyl)acrylamide (1l), 1n, (E)-3-(4-chlorophenyl)-N-cyclohexil-N-(cyclohexylcarbamoyl)acrylamide (5a), 13h and 13i have potential to act as possible inhibitors of histone deacetylase proteins particularly HDAC4 and HDAC8.

Situé au sein de la plaine de la Bekaa au Liban, le fleuve du Litani est sujet à divers rejets agricoles, industriels, domestiques et urbain. Lors de l'irrigation des parcelles agricoles, les eaux du fleuve contaminent le sol et les cultures présentant ainsi un risque pour la santé de l'Homme et l’environnement. Parmi les méthodes de remédiation émergentes et en adéquation avec le développement durable figure la phytoremédiation assistée par les champignons mycorhiziens arbusculaires (CMA). Cependant, la rentabilité de ce mode de gestion constitue l'un des principaux freins à son développement et la valorisation de produits biosourcés, à hautes valeurs ajoutées, issus de la biomasse végétale produite sur ces sols contaminés permettrait d'abaisser les coûts globaux de gestion et de requalification de ces sols pollués. Parmi les filières de valorisation éco-innovantes, la culture de plantes à parfums aromatiques et médicinales (PPAM) productrices d'huiles essentielles (HE) à activités biologiques peut être suggérée comme une option prometteuse. Ainsi, l'objectif de ce travail de thèse a consisté tout d'abord à caractériser le sol d'une parcelle expérimentale située à Marj-Bekaa et directement irriguée par les eaux du Litani, puis à proposer un mode de gestion basé sur la production d'HE pouvant ainsi répondre aux attentes environnementales, économiques et sociales. Nos résultats montrent que la parcelle expérimentale, située à Marj-Bekaa et directement irriguée par les eaux du Litani, est principalement contaminée par des éléments traces métalliques [Ni (88 mg.Kgˉ ¹), Cr (122 mg.Kgˉ ¹), V (170 mg.Kgˉ ¹) et Mn (551 mg.Kgˉ ¹) et des polluants organiques [les alcanes (2.5 g.Kgˉ ¹ du sol)]. Cette contamination est à l'origine d'une (1) cytotoxicité vis-à-vis des cellules pulmonaires et hépatiques mise en évidence grâce au dosage de deux activités enzymatiques, la lactate déshydorgénase et la déshydorgénase mithochondriale mais aussi d'une (2) écotoxicité révélée par la réduction (i) des taux de germination des graines (blé, trèfle, luzerne, ray-grass et fétuque), (ii) de la biomasse microbienne du sol [bactéries Gram-positive et Gram-négative, champignons mychoriziens à arbuscules (CMA), champignons saprotrophes et ectomycorhiziens], (iii) de l'abondance et de la diversité des spores de CMA et (iv) de la richesse et de la diversité végétales. Cependant, toutes les plantes indigènes étaient mycorhizées. C'est pourquoi, la faisabilité de la phytoremédiation assistée par les CMA du site expérimental de la Bekaa, a été testée à la fois en microcosmes et in situ en utilisant une plante aromatique productrice d'HE, l'origan (Origanum syriacum L.). Nos résultats ont montré que non seulement l'origan possède un potentiel de dissipation des alcanes mais en plus cette plante ne transfère pas ces polluants dans les HE extraites à partir de sa biomasse aérienne. Par ailleurs, il a été constaté que la mycorhization a une influence sur la composition des HE. En outre, notre étude a permis l'évaluation de diverses activités biologiques (antifongiques, antioxydante et anti-inflammatoire) d'une gamme d'HE extraites de différentes espèces végétales dont l'origan et ce en présence et en absence des cyclodextrines (HP-β-CD), oligosaccharides cycliques qui complexent les HE et augmentent leurs biodisponibilités. / Located in the Bekaa valley in Lebanon, The Litani River is exposed to agricultural, industrial, domestic and urban wastewaters. Through the irrigation of agricultural soils, the river's water contributes to soil and culture contamination and represents a risk for human health and environment. Amongst the emergent sustainable remediation methods, there is arbuscular mycorrhizal fungi (AMF) assisted-phytoremediation. However, one of the limitation in using phytoremediation as depollution method is its socio-economic profitability. Among the eco-innovative valorization processes with high profitability, the cultivation of aromatic and medicinal plants producing essential oils (EO) with biological activities has been suggested as a promising option. Thus, this thesis work aims firstly at characterizing the soil of an experimental site located at Marj-Bekaa and directly irrigated by the Litani's water and secondly at proposing a mode of management of the contaminated soil based on the production of EO that can meet environmental, economic and social expectations. Our findings showed that the soil sampled in Marj-Bekaa is mainly contamined by metal trace elements [Ni (88 mg.Kgˉ ¹), Cr (122 mg.Kgˉ ¹), V (170 mg.Kgˉ ¹) and Mn (551 mg.Kgˉ ¹) and alkanes (2.5 g.Kgˉ ¹ of soil). This contamination is causing (i) cytotoxicity against both bronchial and hepatic human cells revealed by the evaluation of two enzyme activities, extracellular lactate dehydrogenase and mitochondrial dehydrogenase, as well as (2) ecotoxicity pointed out by the reduction of (i) seed germination (wheat, clover, alfalfa, ryegrass and tall fescue), (ii) soil microbial biomass [Gram-positive and Gram-negative bacteria, arbuscular mycorrhizal fungal (AMF), ectomycorrhizal and saprotrophic fungi], (iii) abundance and diversity of AMF spores as well as (iv) the plant diversity and richness. The AMF-assisted phytoremediation of the Bekaa experimental site was evaluated both in microcosms and in situ experiments using an aromatic plant producing EO, oregano (Origanum syriacum L.). Our results revealed that oregano plant possess an alkane's dissipation potential and no polluant transfer is detected in EO. Moreover, the mycorrhization modified the EO composition. On the over hand, our study evaluated several biological (antifungal, antioxidant and anti-inflammatory) activities of a range of EO extracted from many plant species including oregano, in the presence and the absence of cyclodextrines (HP-β-CD), cyclic oligosaccharides that encapsulate EO and enhance their bioavailabilities.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / In this study, methanolic and acid methanolic extracts were prepared from the aerial parts of Leonurus sibiricus L. and six secondary metabolites were isolated: the triterpene squalene (28), the labdane-type diterpenoid leojaponin (29), the phytosterols β-sitosterol (30) and β-sitosterol glycosylated (32), the bis phthalate (2-ethylhexyl) (31) and the alkaloid leunurina (1), which are unprecedented in this species with the exception of alkaloid 1. These isolated compounds were tested to determine their antimicrobial activity and enzyme inhibition against to acetylcholinesterase (AChE) and proliloligopeptidase (POP) enzymes. The obtained results indicated moderate antimicrobial potential of the tested samples. The leojaponin diterpene (29) showed better results in the POP inhibition assay, with 72%. Regarding the assay of AChE enzyme, the metabolites tested demonstrated inhibition potential with percentages between 10-17%. Furthermore, in order to evaluate different methods of obtaining the methanolic and acid methanolic extracts, a serie of L. sibiricus extracts were prepared to compare yields, chromatographic profile and biological activities thereof. According to the observed results, the highest yield was obtained by hot extraction using reflux method and MeOH/HCl 1% as an extraction solvent (EB q-MeOH +, 21% yield). All acid extracts showed greater potential for enzyme inhibition, with the highest percentage obtained for the extracts from extraction assisted by ultrasound EB CHII-MeOH+ and CHI-MeOH+ (sonoreator like cup horn) and EB USII-MeOH+ (ultrasonic bath), with 91, 80 and 84% inhibition of POP enzyme, respectively. Considering the AChE, the highest percentages of inhibition were also obtained with extracts prepared by ultrasound technology (EB USI-MeOH and USI-MeOH+ with 34 and 38% of AChE inhibition, respectively). Moreover, it was carried out the extraction of essential oil from the fresh aerial parts of L. sibiricus to determine their chemical composition and biological activity. Three main constituents of the oil were identified: trans-caryophyllene (31.7%), α-humulene (18.53%) and γ-muuruleno (19.12%). The oil did not show satisfactory results for its biological activity in all performed tests. / No presente trabalho foram preparados os extratos metanólico e metanólico ácido das partes aéreas de Leonurus sibiricus L. e isolados seis metabólitos secundários: o triterpeno esqualeno (28), o diterpeno do tipo labdano leojaponina (29), os fitoesteróis β-sitosterol (30) e β-sitosterol glicosilado (32), o ftalato de bis (2-etilexila) (31) e o alcaloide leonurina (1), inéditos nesta espécie com excessão do alcaloide 1. Estes compostos isolados foram testados a fim de se determinar suas atividades antimicrobiana e de inibição enzimática frente às enzimas acetilcolinesterase (AChE) e prolil oligopeptidase (POP). Os resultados obtidos indicaram moderado potencial antimicrobiano das amostras testadas. O diterpeno leojaponina (29) apresentou melhor resultado no ensaio de inibição da POP, com 72%. Com relação ao ensaio de inibição da enzima AChE, os metabólitos testados demonstraram um potencial de inibição com percentuais entre 10-17%. Além disso, objetivando-se avaliar diferentes métodos de obtenção dos extratos brutos metanólico e metanólico ácido foram preparados uma série de extratos de L. sibiricus a pequena escala a fim de se comparar rendimentos, perfis cromatográficos e atividades biológicas dos mesmos. De acordo com os resultados observados, o maior rendimento foi obtido através da extração a quente utilizando refluxo e MeOH/HCl 1% como solvente de extração (EB q-MeOH+; com 21% de rendimento). Todos os extratos ácidos apresentaram maior potencial de inibição enzimática, sendo os maiores percentuais obtidos para os extratos provenientes de extrações asistidas por ultrassom EB CHII-MeOH+ e CHI-MeOH+ (sonoreator do tipo cup horn ) e USII-MeOH+(banho ultrassonico), com 91, 80 e 84% de inibição da enzima POP, respectivamente. Em relação a AChE, os maiores percentuais de inibição também foram obtidos com os extratos preparados por tecnologia de ultrassom (EB USI-MeOH e USI-MeOH+ com 34 e 38% de inibição da AChE, respectivamente). Realizou-se ainda a extração do óleo essencial das partes aéreas frescas de L. sibiricus a fim de determinar sua composição química e atividade biológica. Foram identificados três constituintes principais do óleo: trans-cariofileno (31,7%), α-humuleno (18,53%) e γ-muuruleno (19,12%). O óleo não apresentou resultados satisfatórios quando a sua atividade biológica, em todos os testes realizados.

The present study was designed to evaluate the biological activity from the stem bark of Zanthoxylum rhoifolium and Zanthoxylum hyemale. The neutral methanol extract and fractions of this extract, the basic fractions that were obtained after acid-basic extraction from the methanolic extract, and pure compounds isolated from these fraction, were investigated in vitro for antimicrobial activity, antioxidant potential and for acetylcholinesterase inhibition. From the dichlorometane fraction of Zanthoxylum rhoifolium were isolated three furoquinoline alkaloids: skimianine, 8-hidroxy-4,7-dimetoxy-furoquinoline, and γ-fagarin, four benzophenantridine alkaloids: dihydrocheleritrine, dihydroavicine, zanthoxyline and cheleritrine. From the hexane fraction, the lignanes sesamine and lupeol were also isolated. From the neutral methanol extract were isolates de aporfinic alkaloid magnoflorine. The minimal inhibitory concentration of cheleritrine (MIC =1.50 μg/ml) for all tested bacteria, and between 3.12 and 12.5 μg/ml for the tested yeasts, showed this alkaloid have a excellent antimicrobial activity compared to chloramphenicol (between 3.5 to 6.25 μg/m for bacteria) and nistatin (between 5.5 to 10.3 μg/ml for yeasts). The study highlighted the antimicrobial activity of Z. rhoifolium stem bark. This activity is probably due their higher benzophenantridinic alkaloids level. The furoquinoline alkaloids, despite their insignificant antimicrobial activity, were the most active against the enzime AChE. In addition, in this work, the amide tembamide was isolated from the steam bark of Zanthoxylum hyemale, and their derivatives used for a structure-ativity analysis. / O presente estudo foi proposto para avaliar a atividade biológica da casca do caule de Zanthoxylum rhoifolium e Zanthoxylum hyemale. O extrato metanólico neutro e as frações deste extrato, as frações básicas obtidas após extração ácido-base do extrato metanólico e os compostos puros isolados dessas frações, foram avaliados in vitro quanto a atividade antimicrobiana, potencial antioxidante e inibição da enzima acetilcolinesterase. Da fração diclorometânica de Zanthoxylum rhoifolium foram isolados três alcalóides furoquinolínicos: skimianina, 8-hidroxi-4,7-dimetoxi-furoquinolinico e γ-fagarina, quatro alcalóides benzofenantridínicos: diidrocheleritrina, diidroavicina, zantoxilina e cheleritrina. Da fração hexânica foram isolados a lignana sesamina e o triterpeno lupeol. A partir do extrato metanólico neutro foi isolado o alcalóide aporfinico magnoflorina. A concentração inibitória mínima de cheleritrina (CIM = 1,50 μg/ml) para todas as bactérias testadas, e entre 3,12 e 12,5 μg/ml para as leveduras testadas, mostraram que este alcalóide possui uma excelente atividade antimicrobiana em comparação ao cloranfenicol (entre 3,5-6,25 μg/ml para as bactérias) e nistatina (entre 5,5-10,3 μg/ml para as leveduras). O estudo evidenciou a atividade antimicrobiana da casca do caule de Z. rhoifolium. Esta atividade é, provavelmente, devido ao seu alto nível de alcalóides benzofenantridínicos. Os alcalóides furoquinolinicos, mostraram pequena atividade antimicrobiana e foram os mais ativos frente a enzima AChE. Além disso, neste trabalho, a amida tembamida foi isolada da casca do caule de Zanthoxylum hyemale e seus derivados utilizados para uma análise de relação estrutura-atividade.